The project is based on characterization and application of improved techniques to evaluate binding of agonist-ligands to presumed dopamine (DA) receptors in membranes preparations of animal brain tissue. The in vitro pharmacology and biochemistry of the binding of tritiated catechol-aporphines is being compared with that of labeled DA and its rigid analogs, such as dihydroxyaminotetralins (ADTNs). The tissue preparations used permit unprecedented levels of displaceable or saturable (so-called "specific" binding) to be evaluated with tritium-labeled aporphines. The effects of temperature, pH, ions, nucleotides; the distribution and kinetics; as well as the pharmacology and structure-activity relationships of large series of analogs and drugs are being evaluated for their interactions with such binding. Characteristics of binding of such agonists is compared with that of labeled antagonists, such as tritiated spiroperidol. Attempts are made to evaluate differentiating characteristics of agonist vs. antagonists binding sites, for example by evaluating rates of denaturation at elevated temperatures. Effects of development and aging, of sex and steroid hormones, and of selective brain lesions (with selective neurotoxins and by vascular and surgical lesions of cortex) on ligand binding will be evaluated. Effects of prolonged exposure to antipsychotic and mood-altering drugs on receptors will be followed over time. Correlations will be sought between selected genetically and behaviorally dissimilar rodent strains and DA receptor kinetics. Binding assays will be applied to measurements of tissue levels of catecholaporphines and compared with independent biochemical assay and with behavioral changes with varying doses and times.